The presence of a 1.4 x 10 to the 6th power dalton double-stranded RNA in intracellular virus-like particles (the K1 killer plasmid or killer virus) in Saccharomyces cerevisiae enables cells to secrete a protein toxin and be immune to this toxin. We have defined 29 chromosomal genes (called mak1, . . .) needed to replicate the killer plasmid and 5 regulatory chromosomal genes affecting the killer plasmid (ski genes, KRB1). A second killer plasmid, called K2, is excluded by the K1 plasmid. We have found a new plasmid, called (EXL), which is not a killer plasmid but also excludes K2. Yet another plasmid, called (NEX), prevents this effect of (EXL) on K2. A chromosomal gene, mkt1, is required for K2 maintenance if (NEX) is present. A third new yeast plasmid, (HOK), acts as a helper for a replication-defective mutant of the K1 killer plasmid. (EXL), (NEX), and (HOK) each depend on various MAK genes for their replication.